Bone invading NSCLC cells produce IL-7: Mice model and human histologic data

Ilaria Roato, Davide Caldo, Laura Godio, Lucia D'Amico, Paolo Giannoni, Emanuela Morello, Rodolfo Quarto, Luigi Molfetta, Paolo Buracco, Antonio Mussa, Riccardo Ferracini

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Abstract

Background: Bone metastases are a common and dismal consequence of lung cancer that is a leading cause of death. The role of IL-7 in promoting bone metastases has been previously investigated in NSCLC, but many aspects remain to be disclosed. To further study IL-7 function in bone metastasis, we developed a human-in-mice model of bone aggression by NSCLC and analyzed human bone metastasis biopsies.Methods: We used NOD/SCID mice implanted with human bone. After bone engraftment, two groups of mice were injected subcutaneously with A549, a human NSCLC cell line, either close or at the contralateral flank to the human bone implant, while a third control group did not receive cancer cells. Tumor and bone vitality and IL-7 expression were assessed in implanted bone, affected or not by A549. Serum IL-7 levels were evaluated by ELISA. IL-7 immunohistochemistry was performed on 10 human bone NSCLC metastasis biopsies for comparison.Results: At 12 weeks after bone implant, we observed osteogenic activity and neovascularization, confirming bone vitality. Tumor aggressive cells implanted close to human bone invaded the bone tissue. The bone-aggressive cancer cells were positive for IL-7 staining both in the mice model and in human biopsies. Higher IL-7 serum levels were found in mice injected with A549 cells close to the bone implant compared to mice injected with A549 cells in the flank opposite to the bone implant.Conclusions: We demonstrated that bone-invading cells express and produce IL-7, which is known to promote osteoclast activation and osteolytic lesions. Tumor-bone interaction increases IL-7 production, with an increase in IL-7 serum levels. The presented mice model of bone invasion by contiguous tumor is suitable to study bone-tumor cell interaction. IL-7 plays a role in the first steps of metastatic process.

Original languageEnglish
Article number12
JournalBMC Cancer
Volume10
DOIs
Publication statusPublished - Jan 12 2010

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Interleukin-7
Bone and Bones
Neoplasm Metastasis
mouse interleukin-7
Neoplasms
Biopsy
Serum
Bone Neoplasms
Inbred NOD Mouse
SCID Mice
Osteoclasts
Aggression
Cell Communication
Cause of Death
Lung Neoplasms
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

Cite this

Roato, I., Caldo, D., Godio, L., D'Amico, L., Giannoni, P., Morello, E., ... Ferracini, R. (2010). Bone invading NSCLC cells produce IL-7: Mice model and human histologic data. BMC Cancer, 10, [12]. https://doi.org/10.1186/1471-2407-10-12

Bone invading NSCLC cells produce IL-7 : Mice model and human histologic data. / Roato, Ilaria; Caldo, Davide; Godio, Laura; D'Amico, Lucia; Giannoni, Paolo; Morello, Emanuela; Quarto, Rodolfo; Molfetta, Luigi; Buracco, Paolo; Mussa, Antonio; Ferracini, Riccardo.

In: BMC Cancer, Vol. 10, 12, 12.01.2010.

Research output: Contribution to journalArticle

Roato, I, Caldo, D, Godio, L, D'Amico, L, Giannoni, P, Morello, E, Quarto, R, Molfetta, L, Buracco, P, Mussa, A & Ferracini, R 2010, 'Bone invading NSCLC cells produce IL-7: Mice model and human histologic data', BMC Cancer, vol. 10, 12. https://doi.org/10.1186/1471-2407-10-12
Roato I, Caldo D, Godio L, D'Amico L, Giannoni P, Morello E et al. Bone invading NSCLC cells produce IL-7: Mice model and human histologic data. BMC Cancer. 2010 Jan 12;10. 12. https://doi.org/10.1186/1471-2407-10-12
Roato, Ilaria ; Caldo, Davide ; Godio, Laura ; D'Amico, Lucia ; Giannoni, Paolo ; Morello, Emanuela ; Quarto, Rodolfo ; Molfetta, Luigi ; Buracco, Paolo ; Mussa, Antonio ; Ferracini, Riccardo. / Bone invading NSCLC cells produce IL-7 : Mice model and human histologic data. In: BMC Cancer. 2010 ; Vol. 10.
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abstract = "Background: Bone metastases are a common and dismal consequence of lung cancer that is a leading cause of death. The role of IL-7 in promoting bone metastases has been previously investigated in NSCLC, but many aspects remain to be disclosed. To further study IL-7 function in bone metastasis, we developed a human-in-mice model of bone aggression by NSCLC and analyzed human bone metastasis biopsies.Methods: We used NOD/SCID mice implanted with human bone. After bone engraftment, two groups of mice were injected subcutaneously with A549, a human NSCLC cell line, either close or at the contralateral flank to the human bone implant, while a third control group did not receive cancer cells. Tumor and bone vitality and IL-7 expression were assessed in implanted bone, affected or not by A549. Serum IL-7 levels were evaluated by ELISA. IL-7 immunohistochemistry was performed on 10 human bone NSCLC metastasis biopsies for comparison.Results: At 12 weeks after bone implant, we observed osteogenic activity and neovascularization, confirming bone vitality. Tumor aggressive cells implanted close to human bone invaded the bone tissue. The bone-aggressive cancer cells were positive for IL-7 staining both in the mice model and in human biopsies. Higher IL-7 serum levels were found in mice injected with A549 cells close to the bone implant compared to mice injected with A549 cells in the flank opposite to the bone implant.Conclusions: We demonstrated that bone-invading cells express and produce IL-7, which is known to promote osteoclast activation and osteolytic lesions. Tumor-bone interaction increases IL-7 production, with an increase in IL-7 serum levels. The presented mice model of bone invasion by contiguous tumor is suitable to study bone-tumor cell interaction. IL-7 plays a role in the first steps of metastatic process.",
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AU - Roato, Ilaria

AU - Caldo, Davide

AU - Godio, Laura

AU - D'Amico, Lucia

AU - Giannoni, Paolo

AU - Morello, Emanuela

AU - Quarto, Rodolfo

AU - Molfetta, Luigi

AU - Buracco, Paolo

AU - Mussa, Antonio

AU - Ferracini, Riccardo

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N2 - Background: Bone metastases are a common and dismal consequence of lung cancer that is a leading cause of death. The role of IL-7 in promoting bone metastases has been previously investigated in NSCLC, but many aspects remain to be disclosed. To further study IL-7 function in bone metastasis, we developed a human-in-mice model of bone aggression by NSCLC and analyzed human bone metastasis biopsies.Methods: We used NOD/SCID mice implanted with human bone. After bone engraftment, two groups of mice were injected subcutaneously with A549, a human NSCLC cell line, either close or at the contralateral flank to the human bone implant, while a third control group did not receive cancer cells. Tumor and bone vitality and IL-7 expression were assessed in implanted bone, affected or not by A549. Serum IL-7 levels were evaluated by ELISA. IL-7 immunohistochemistry was performed on 10 human bone NSCLC metastasis biopsies for comparison.Results: At 12 weeks after bone implant, we observed osteogenic activity and neovascularization, confirming bone vitality. Tumor aggressive cells implanted close to human bone invaded the bone tissue. The bone-aggressive cancer cells were positive for IL-7 staining both in the mice model and in human biopsies. Higher IL-7 serum levels were found in mice injected with A549 cells close to the bone implant compared to mice injected with A549 cells in the flank opposite to the bone implant.Conclusions: We demonstrated that bone-invading cells express and produce IL-7, which is known to promote osteoclast activation and osteolytic lesions. Tumor-bone interaction increases IL-7 production, with an increase in IL-7 serum levels. The presented mice model of bone invasion by contiguous tumor is suitable to study bone-tumor cell interaction. IL-7 plays a role in the first steps of metastatic process.

AB - Background: Bone metastases are a common and dismal consequence of lung cancer that is a leading cause of death. The role of IL-7 in promoting bone metastases has been previously investigated in NSCLC, but many aspects remain to be disclosed. To further study IL-7 function in bone metastasis, we developed a human-in-mice model of bone aggression by NSCLC and analyzed human bone metastasis biopsies.Methods: We used NOD/SCID mice implanted with human bone. After bone engraftment, two groups of mice were injected subcutaneously with A549, a human NSCLC cell line, either close or at the contralateral flank to the human bone implant, while a third control group did not receive cancer cells. Tumor and bone vitality and IL-7 expression were assessed in implanted bone, affected or not by A549. Serum IL-7 levels were evaluated by ELISA. IL-7 immunohistochemistry was performed on 10 human bone NSCLC metastasis biopsies for comparison.Results: At 12 weeks after bone implant, we observed osteogenic activity and neovascularization, confirming bone vitality. Tumor aggressive cells implanted close to human bone invaded the bone tissue. The bone-aggressive cancer cells were positive for IL-7 staining both in the mice model and in human biopsies. Higher IL-7 serum levels were found in mice injected with A549 cells close to the bone implant compared to mice injected with A549 cells in the flank opposite to the bone implant.Conclusions: We demonstrated that bone-invading cells express and produce IL-7, which is known to promote osteoclast activation and osteolytic lesions. Tumor-bone interaction increases IL-7 production, with an increase in IL-7 serum levels. The presented mice model of bone invasion by contiguous tumor is suitable to study bone-tumor cell interaction. IL-7 plays a role in the first steps of metastatic process.

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